Sirtuin 6 Expression and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Incretin Treatment
Sirtuin 6 Expression and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Incretin Treatment
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DOI：
10.2337/db14-1149
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发表时间：
2015-04-01
期刊：
影响因子：
7.7
通讯作者：
Marfella, Raffaele
中科院分区：
文献类型：
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作者：
Balestrieri, Maria Luisa;Rizzo, Maria Rosaria;Marfella, Raffaele
sirtuin 6（SIRT 6）在糖尿病患者动脉粥样硬化进展中的作用尚不清楚。我们评估了SIRT 6的表达和基于肠促胰岛素的治疗对无症状糖尿病和非糖尿病患者颈动脉斑块的影响。斑块来自52例2型糖尿病患者和30例接受颈动脉内膜切除术的非糖尿病患者。22例糖尿病患者在接受动脉内膜切除术前接受了26 +/- 8个月的肠促胰岛素系统药物、GLP-1受体激动剂和二肽基肽酶-4抑制剂治疗。与非糖尿病斑块相比，糖尿病斑块具有更多的炎症和氧化应激，沿着较少的SIRT 6表达和胶原含量。与非GLP-1治疗的斑块相比，GLP-1治疗的斑块表现出更高的SIRT 6表达和胶原蛋白含量，以及更少的炎症和氧化应激，表明斑块表型更稳定。这些结果得到了内皮祖细胞（EPCs）和内皮细胞（ECs）体外观察的支持。事实上，与仅用高葡萄糖处理的细胞相比，在存在GLP-1（100 nmol/L利拉鲁肽）的情况下用高葡萄糖（25 mmol/L）处理的EPC和EC均表现出更高的SIRT 6表达和更低的核因子B表达。这些发现确立了SIRT 6参与糖尿病动脉粥样硬化病变的炎症途径，并表明肠促胰岛素可能对其进行积极调节，其作用与潜在稳定斑块表型的形态和组成特征相关。
The role of sirtuin 6 (SIRT6) in atherosclerotic progression of diabetic patients is unknown. We evaluated SIRT6 expression and the effect of incretin-based therapies in carotid plaques of asymptomatic diabetic and nondiabetic patients. Plaques were obtained from 52 type 2 diabetic and 30 nondiabetic patients undergoing carotid endarterectomy. Twenty-two diabetic patients were treated with drugs that work on the incretin system, GLP-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors for 26 +/- 8 months before undergoing the endarterectomy. Compared with nondiabetic plaques, diabetic plaques had more inflammation and oxidative stress, along with a lesser SIRT6 expression and collagen content. Compared with non-GLP-1 therapy-treated plaques, GLP-1 therapy-treated plaques presented greater SIRT6 expression and collagen content, and less inflammation and oxidative stress, indicating a more stable plaque phenotype. These results were supported by in vitro observations on endothelial progenitor cells (EPCs) and endothelial cells (ECs). Indeed, both EPCs and ECs treated with high glucose (25 mmol/L) in the presence of GLP-1 (100 nmol/L liraglutide) presented a greater SIRT6 and lower nuclear factor-B expression compared with cells treated only with high glucose. These findings establish the involvement of SIRT6 in the inflammatory pathways of diabetic atherosclerotic lesions and suggest its possible positive modulation by incretin, the effect of which is associated with morphological and compositional characteristics of a potential stable plaque phenotype.